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Roles of the NF-κB Pathway in B-Lymphocyte Biology

  • Yoshiteru SasakiEmail author
  • Kazuhiro Iwai
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 393)

Abstract

NF-κB was originally identified as a family of transcription factors that bind the enhancer of the immunoglobulin κ light-chain gene. Although its function in the regulation of immunoglobulin κ light-chain gene remains unclear, NF-κB plays critical roles in development, survival, and activation of B lymphocytes. In B cells, many receptors, including B-cell antigen receptor (BCR), activate NF-κB pathway, and the molecular mechanism of receptor-mediated activation of IκB kinase (IKK) complex has been partially revealed. In addition to normal B lymphocytes, NF-κB is also involved in the growth of some types of B-cell lymphomas, and many oncogenic mutations involved in constitutive activation of the NF-κB pathway were recently identified in such cancers. In this review, we first summarize the function of NF-κB in B-cell development and activation, and then describe recent progress in understanding the molecular mechanism of receptor-mediated activation of the IKK complex, focusing on the roles of the ubiquitin system. In the last section, we describe oncogenic mutations that induce NF-κB activation in B-cell lymphoma.

Keywords

Polyubiquitin Chain Ubiquitin System MyD88 L265P Linear Ubiquitin Chain Ubiquitin Conjugation System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

CBM

CARMA1–BCL10–MALT1

CSR

Class-switch recombination

CYLD

Cylindromatosis

DAG

Diacylglycerol

DUB

Deubiquitinating enzyme

GC

Germinal center

IκB

Inhibitor of nuclear factor-κB

ITAM

Immunoreceptor tyrosine-based activation motifs

IKK

IκB kinase

LUBAC

Linear ubiquitin chain assembly complex

NEMO

NF-κB essential modifier

NF-κB

Nuclear factor-κB

NIK

NF-κB-inducing kinase

OTU

Ovarian tumor domain

OTULIN

OTU DUB with linear linkage specificity

PKC

Protein kinase C

TD

Thymus-dependent

TI

Thymus-independent

TLR

Toll-like receptor

TRAF

TNF receptor-associated factor

UBAN

Ubiquitin binding in ABIN proteins and NEMO

WT

Wild type

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Authors and Affiliations

  1. 1.Department of Molecular and Cellular Physiology, Graduate School of MedicineKyoto UniversityKyotoJapan

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